Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma

Purpose: A first comparative trial of fludarabine (FLU) alone versus FLU pl us idarubicin (FLU-ID) for indolent or mantle-cell lymphomas. Patient and Methods: From September 1995 to July 1998, 199 patients aged 25 to 65 years (median, 54 years) with newly diagnosed stages II to IV indole nt or mantle-cell lymphomas (standard risk according to the International P rognostic Index) were enrolled onto a multicenter, 1:1 randomized study. Of the 199 patients who were able ta be assessed, 101 were assigned to the FL U group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 5) and 98 to the FLU-ID group (six monthly cycles of FLU 25 mg/m2/d on days 1 throug h 3 and idarubicin 12 mg/m(2) on day 1). Results: In the FLU group, complete response (CR) and partial response rate s were 47% and 37%, respectively, whereas in the FLU-ID group, they were 39 % and 42%, respectively. In depth analysis of the CR rate with respect to h istologic type showed that FLU seemed to be superior to FLU-ID in treating follicular lymphomas (60% v 40%, respectively), whereas FLU-ID seemed be mo re effective than FLU in treating nonfollicular lymphomas (small lymphocyti c, 43% v 29%, respectively; immunocytoma, 38% v 23%, respectively; P = not significant), excluding the mantle-cell subset (in which there was no diffe rence between the two groups). No striking differences were observed betwee n the two protocols in terms of overall response or toxicity, which was gen erally mild. However, with ct median follow-vp of 19 months, only 29 patien ts (62%) who received FLU alone have maintained their initial CR, compared with 32 (84%) of those who received FLU-ID therapy (P = .021), Conclusion: Although the FLU-ID regimen may not significantly improve the i nduction of CR in most indolent-lymphoma patients, our preliminary data do suggest that, with respect to FLU alone, it may be capable of conferring a longer-lasting CR and that it might be superior in terms of CR rate in smal l lymphocytic and immunocytoma subtypes. (C) 2000 by American Society of Cl inical Oncology.